Research progress on treatment strategies for related diseases based on Parthanatos / 中国生物制品学杂志

@#Parthanatos is a form of programmed cell death,which is also known as poly(ADP-ribose)polymerase 1(PARP1)-mediated apoptosis-inducing factor(AIF)and macrophage migration inhibitory factor(MIF)-dependent cell death according to its molecular mechanism. Parthanatos is the main cause of a variety of neurodegenerative diseases,such as Parkinson's disease(PD),Alzheimer's disease(AD),motor neuron disease,and is also involved in the pathogenesis of some tumors,such as lung cancer and breast cancer. Therefore,a thorough understanding of the molecular mechanism of Parthanatos is crucial for the therapeutic strategies of related diseases. In recent years,studies have found that effective regulation of the occurrence of Parthanatos by regulating the key proteins PARP1,AIF and MIF is expected to become a therapeutic target for many diseases. Based on the specific molecular mechanism of Parthanatos,this paper reviewed the research progress of therapeutic strategies for related diseases from the aspects of inhibiting and promoting Parthanatos.

Advances in researches on mechanism of macrophage migration inhibitory factor regulating parasite-host immune interaction / 中国血吸虫病防治杂志

Macrophage migration inhibitory factor (MIF), a type of pleiotropic immunoregulatory cytokine with a specific structure, participates in the regulation of host cell growth and migration and immune responses. Following parasitic infections, hosts may produce MIF and then participate in the parasite-host interactions. In addition, parasites may secrete parasite-derived MIF, and they jointly participate in parasite-host interactions. This paper reviews the regulation of MIF gene expression following parasitic infections, the role of MIF in parasite-host immune system interactions, and important signaling pathways of MIF-mediated immune responses.

Advances in researches on mechanism of macrophage migration inhibitory factor regulating parasite-host immune interaction / 中国血吸虫病防治杂志

Macrophage migration inhibitory factor (MIF), a type of pleiotropic immunoregulatory cytokine with a specific structure, participates in the regulation of host cell growth and migration and immune responses. Following parasitic infections, hosts may produce MIF and then participate in the parasite-host interactions. In addition, parasites may secrete parasite-derived MIF, and they jointly participate in parasite-host interactions. This paper reviews the regulation of MIF gene expression following parasitic infections, the role of MIF in parasite-host immune system interactions, and important signaling pathways of MIF-mediated immune responses.

Efficacy of Yanhuning injection in the treatment of acute viral myocarditis with Xiedu Qinxin syndrome / 中国基层医药

Objective To investigate the effect of Yanhuning injection antiviral therapy in the treatment of acute viral myocarditis patients with Xiedu Qinxin syndrome.Methods From May 2016 to August 2017,84 acute viral myocarditis patients with Xiedu Qinxin syndrome in the Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou were enrolled in this study.According to the digital table,they were randomly divided into observation group and the control group,with 42 cases in each group.The control group received conventional antiviral therapy,and the observation group was given Yanhuning injection.The heart type free fatty acid binding protein (H－FABP),serum troponin Ⅰ (cTnI),macrophage migration inhibitory factor(MIF)and interleukin 4(IL－4)were measured before and after treatment for 4 weeks.The clinical symptoms score and the effective rate were compared between the two groups at the same time.Results The serum levels of cTnI,H－FABP,MIF and IL－4 of the two groups after treatment were lower than those before treatment(all P＜0.05 ),which of the observation group after treatment were significantly lower than those of the control group (t＝3.012,P＝0.039;t＝2.835,P＝0.040;t＝3.534,P＝0.032;t＝3.323,P＝0.033).The effective rate of the observation group was significantly higher than that of the control group (90.48% vs.80.95%,χ2＝3.432,P＝0.038).The scores of palpitations,sore throat,upsetting the chest tightness of the observation group after treatment were significantly lower than those of the control group (t＝3.045,P＝0.038;t＝2.946,P＝0.039;t＝3.467,P＝0.031;t ＝3.358,P＝0.032).Conclusion Yanhuning injection antiviral therapy in the treatment of acute viral myocarditis patients with Xiedu Qinxin syndrome can signifi-cantly improve the efficacy of patients.

Mifepristone derivative FZU-00,033 suppresses triple-negative breast cancer cell viability via down-regula-ting KLF5 expression / 医学研究生学报

Objective Mifepristone (MIF) can inhibit triple-negative breast cancer cell (TNBC) survival at high concentra-tions. The purpose of the present study is to study the effect of mifepristone derivatives on triple-negative breast cancer cell (TNBC) survival at low concentrations. Methods SUM149PT and HCC1937 triple negative breast cancer cells were used in the study; the experiment was set in four groups: DMSO group,MIF group(10 μmol/L MIF),5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group. They were treated with 24,48,72 h,and cell viability was measured by SRB. KLF5 overexpression HCC1937 cell line was used in the study; the experiment was set in four groups: PCDH-DMSO group(PCDH vector,DMSO),PCDH-FZU-00,033 group (PCDH vector,10 μmol/L FZU-00,033),KLF5-DMSO group(overexpress KLF5,DMSO),KLF5-FZU-00,033 group(overexpress KLF5,10 μmol/L FZU-00,033). Cell apoptosis was investigated by detecting PARP cleavage using Western blot. In order to investi-gate how FZU-00,033 reduced cell viability,we detected KLF5 protein expression after drug treatment. On the basic of the original PC-DH-DMSO group,PCDH-FZU-00,033 group,KLF5-DMSO group and KLF5-FZU-00,033 group,5 μmol/L PCDH-FZU-00,033 group (PCDH vector,5 μmol/L FZU-00,033),5 μmol/L KLF5-FZU-00,033 group(overexpress KLF5,5 μmol/L FZU-00,033). Western blot was used to detect the effect of FZU-00,033 in KLF5 overexpression cell line. Results Compared with DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group decreasd TNBC cell viability more efficiently at 24,48,72h (P<0.01); the cell survival rate of DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group was [(100±4)%,(17±2)%,(5±1)%,(58±1)%] respectively in SUM149PT cell line and was [(100±7)%,(39±1)%,(30±1)%,(62±1)%] respectively in HCC1937 cell line. Compared with MIF group,5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group decreasd TNBC cell viability more efficiently at 24,48,72 h (P<0.01). Compared with DMSO group,5 μmol/L FZU-00,033 group,10 μmol/L FZU-00,033 group and MIF group suppressed KLF5 expression more potently and increased cell apoptosis. Com-pared with 10 μmol/L MIF group,5 μmol/L FZU-00,033 group and 10 μmol/L FZU-00,033 group significantly increased apoptosis. Compared with PCDH-DMSO group,10 μmol/L PCDH-FZU-00,033 group decreasd TNBC cell viability more efficiently at 48,72 h and cell survial rate was [(100±6)% vs (39±2)%,P<0.05] and [(100±3)% vs (21±1)%,P<0.05] respectively. Compared with KLF5-DMSO group,10 μmol/L KLF5-FZU-00,033 group decreasd TNBC cell viability more efficiently at 48,72h and cell survial rate was [(100±1)% vs (47±1)%,P<0.05] and [(100±1)% vs (27±1)%,P<0.05] respectively; Meanwhile,Compared with 10 μmol/L PCDH-FZU-00,033 group,10 μmol/L KLF5-FZU-00,033 group increased TNBC cell viability more efficiently at 48,72 h (P<0.05). Compared with PCDH-DMSO group,5 μmol/L PCDH-FZU-00,033 group and 10 μmol/L PCDH-FZU-00,033 group in-creased cell apoptosis; Compared with KLF5-DMSO group,5 μmol/L KLF5-FZU-00,033 group and 10 μmol/L KLF5-FZU-00,033 group increased cell apoptosis. Conclusion Novel mifepristone derivative FZU-00,033 suppressed TNBC cell viability partially through suppressing KLF5 expression.

Expression and Clinical Significance of Macrophage Migration Inhibitory Factor in the Serum and Lung Tissues in Patients with Non-Small Cell Lung Cancer / 中山大学学报(医学科学版)

[Objective]To investigate the expression and the clinical significance of macrophage migration inhibitory factor (MIF)in the serum and lung tissues of the patients with non-small cell lung cancer(NSCLC).[Methods]Eighty-eight eligible inpatients were confirmed by pathology of lung tissues ,including 66 patients with NSCLC and 22 patients with benign lung lesions. ELISA was performed to measure serum concentration of MIF of these patients ,which was compared with 30 healthy individuals. Meanwhile,immunohistochemistry(IHC)was performed to examine the expression of MIF in the lung tissues of the two groups. MIF expression level was compared between two groups and among different subgroups of NSCLC. The correlationship between serum MIF level and high expression rate in lung tissues was also analyzed. All the data were analyzed by SPSS17.0.[Results]The serum concentration of MIF in NSCLC group was significantly higher than that in healthy control(14.79 ng/mL vs 10.69 ng/mL,P=0.001), and was slightly higher but not significantly different from benign lung lesions group(14.79 ng/mL vs 13.68 ng/mL,P=0.580). The comparison among subgroups of NSCLC showed that the serum MIF level was not only correlated with the histological grade and clini?cal stage of the cancer,but also correlated with the gender and smoking history of the host. Immunohistochemistry showed that the MIF high expression rate in the lung tissues of NSCLC was markedly higher than that of benign lung lesions group(30.3%vs 4.5%, P=0.014). Among the subgroups of NSCLC,IHC showed MIF high expression rate was correlated with the histopathologic types and clinical stage of the cancer. Simultaneously ,the serum MIF level showed a positive correlation with MIF expression rate in the lung tissues in all patients and NSCLC group(P<0.05).[Conclusion]MIF was strongly related to the clinicopathological characteristics of NSCLC. It could be helpful for the diagnosis and clinical evaluation of NSCLC.

Increased Expression of MIF in Peripheral Blood Mononuclear Cells from Patients with Crytococcal Meningitis and Its Clinical Significance / 现代检验医学杂志

Objective To test the expression of MIF in peripheral blood mononuclear cells (PBMCs)from patients with Cry-tococcal Meningitis and further discuss its clinical significance.Methods Peripheral blood from 42 patients with Crytococcal Meningitis diagnosed in Changhai Hospital,Shanghai and 42 healthy individuals examined at the same time was collected from August,2012 to November,2015.PBMCs were separated by density gradient centrifugation method,mRNA relative expression of MIF in PBMCs was measured by PCR,the level of MIF,IL-17,IL-1β,TNF-α,IFN-γand IL-4 in plasma was tested by Enzyme-linked immunosorbent assay (ELISA).The comparison for expression level of cytokines between the two groups was by two-independent samples t test.Pearson correlation coefficient was used to measure the relation between MIF and other cytokines.Results The protein levels of MIF in experimental and controlled groups were 34.17±7.88 ng/ml vs 10.89±2.76 ng/ml(t=18.07,P<0.0001),while relative expression of RNA was 2.87±0.94 vs 1.95±0.89(t=4.606,P<0.0001),and there was statistical significance (P<0.005).Pearson correlation analysis showed that MIF was positively related with IL-1β,IL-17 (r=0.467,0.401,P<0.01),with statisticaldifference.Conclusion MIF may involve in the im-mune regulation for Crytococcal Meningitis by affecting the secretion and function of cytokines as IL-1β,IL-17,and it was potential target and monitored biomarker for this disease.

Role and mechanism of resveratrol in a rat model of complex regional pain syndrome type Ⅰ / 实用医学杂志

Objective To investigate the role and mechanism of resveratrol in a rat model of complex region-al pain syndrome type Ⅰ(CRPS1). Methods 50 male SD rats were divided into control group(group A),sham operation group(group B),model group 1(group C),model group 2(group D),and model group 3(group E). Groups A,B and C received 5%DMSO;group D received ISO-1 of 1 mg/(kg·d);and group E received resveratrol of 20 mg/(kg · d)for 14 days. Pain behaviors were assessed on days 0,7,and 14. Serum levels of MIF and TNF-αwere detected by ELISA. MIF ,total ERK1/2 and p-ERK1/2 in sciatic nerve were detected by Western blot. Re-sults On days 7 and 14 after treatment,resveratrol injection,similar to ISO-1,significantly improved the pain threshold;serum levels of MIF and TNF-α were significantly decreased;expressions of MIF ,total ERK1/2 and p-ERK1/2 in sciatic nerve were also decreased significantly in group E,which were significantly lower than group C (P < 0.05). Conclusions Resveratrol can significantly improve pain threshold ,decrease expressions of MIF and p-ERK1/2 in a rat model of CRPS1,which might be involved in the inhibition of ERK signaling pathway.

Ubiquitin C-terminal hydrolase 37 promotes the proliferation of colon cancer cells by de-ubiquitinating MIF / 实用医学杂志

Objective To explore the expression and cilinical significance of UCH37 in colon cancer, and detect the effects and underlying mechanism of UCH37 on cell proliferation and cell apoptosis of colon cancer cell lines. Methods Expressions of UCH37 were analyzed by immunohistochemistry in colon cancer patients. Spearman′s rank test was conducted to analyze the clinical relevance of UCH37 in colon cancer. QPCR was conducted to detect the expression of UPS39 in colon cancer cell lines and NCM460 cells.CCK-8,flow cytometry, co-immunoprecipitation were conducted to detect the effects of UCH37 on cell proliferation,cell apoptosis. And ubiquitinated level of MIF. Results Compare to adjacent tissues,immunohistochemistry and chi square analysis revealed that the positive rate of UCH37 was upregulated in colon cancer tissues.Spearman rank correlation showed that positive UCH37 expression was significantly associated with TNM stage and cell differentiation of colon cancer patients. CCK-8 results showed cell proliferation in colon cancer cells transfected with UCH37 NC was promoted and cell apoptosis in colon cancer cells transfected with UCH37 NC was inhibited compared with cells transfected UCH37 siRNAs;furthermore,compared to cells transfected lentiviral vector carrying pLenti6.3.cell proliferation in colon cancer cells transfected with lentiviral vector carrying UCH37 was promoted and cell apoptosis in colon can-cer cells transfected with lentiviral vector carrying UCH37 was inhibited.Co-IP showed MIF could be deubiquitinat-ed by UCH37 in colon cancer cells. Conclusion UCH37 expression is upregulated in colon cancer,and UCH37 could promote cell proliferation of colon cancer cells by deubiquitinating MIF.

Effects of berberine on serum inflammatory factors and carotid atherosclerotic plaques in patients with acute cerebral ischemic stroke / 中国中药杂志

This study aims to analyze the effect of berberine on serum inflammatory factors and carotid atherosclerotic plaques in ppatients with acute cerebral ischemic stroke(AIS). In the study, 120 patients with AIS were randomly divided into berberine group(n=60) and general group (n=60). The 60 cases in the general group were provided with general therapy according to the latest guidelines of diagnosis and treatment of AIS. The berberine group received berberine 300 mg(tid) in addition to the therapy of the general group. The levels of serum inflammatory factors, the nerve function defect grades and the indexes of carotid atherosclerosis plaques [including the total plaque area(TPA), intima-media thickness(IMT) and the number of unstable carotid atherosclerotic plaques] were measured and compared. The results indicated that the levels of serum inflammatory factors, the NIHSS(national institute of health stroke scales) cores and the indexes of carotid atherosclerosis plaques were not significantly different between the berberine groups of general group, with positive correlation between serum inflammatory factors and NIHSS scores(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine groups on 14 d were significantly lower than those on 1 d(P<0.05). The levels of serum inflammatory factors and NIHSS scores of the berberine group on 14 d were significantly lower than those of the general group(P<0.05). The TPA and the number of unstable carotid atherosclerotic plaques of the berberine groups on 90 d were significantly lower than those of general group, with significant differences(P<0.05). The IMT showed a downward trend, but with significant difference.The mRS(modified rankin scale) scores of the berberine group on 90 d were significantly lower, with a higher rate of short-term favorable prognosis (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. This study showed that berberine in addition to the general therapy can significantly lower the levels of serum MIF and IL-6, reduce the degree of carotid atherosclerosis to some extent and improve neurological impairment and the prognosis of patients with AIS.

Effect of angiotensin Ⅱ on the expression of MIF in macrophages / 实用医学杂志

Objective To investigate whether angiotensin Ⅱ (AngⅡ) can regulate the expression of MIF in macrophages via the NF-κB pathway. Methods Western Blot, real time RT-PCR and ELISA were used in the present study. Results Western blot result showed that the expression of NF-κBp65 gradually increased with the increase of the concentration of AngⅡ. Results of real time RT-PCR and ELISA revealed that MIF mRNA expression and the content of MIF were significantly higher in AngⅡ group than those in the control group. PDTC could reverse the effect of AngⅡ on MIF mRNA expression and MIF secretion in macrophages. Conclusion AngⅡ can promote MIF mRNA expression and MIF secretion in macrophages via the NF-κB signaling pathway.

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. .

Research progress on liver injury in acute pancreatitis / 中华肝胆外科杂志

Considerable clinical and experimental evidence supports that liver injury in acute pancreatitis (AP) is a sign for the potential progression to systemic inflammatory reaction.The Kupffer cells,various cytokines and macrophage migration inhibitory factor (MIF) play important roles in the pathogenesis of AP associated liver injury.However,the specific molecular mechanism of the liver damage remains uncertain.Therefore,efforts should be made to clarify the regulatory mechanism and related cell signaling disorders of liver injury in AP,which could not only identify novel therapeutic targets,but also provide new insight into improving the clinical treatment.Here our review discusses the recent research progress on the etiology,pathology and diagnosis and treatments of liver injury in AP.

Expression of MIF in molecular subtypes of breast cancer and its clinical significance / 西安交通大学学报(医学版)

Objective To determine the expression of macrophage migration inhibitory factor (MIF)in different molecular subtypes of breast cancer and its clinical significance so as to detect the biological markers of different molecular subtypes of breast cancer.Methods We divided 100 breast cancer patients into four molecular subtypes by immunostaining:luminal subtype,HER-2(+)subtype,basal-like (BLs)subtype and normal breast-like (NBLs)subtype,and then compared the expression of MIF in the groups.We analyzed the associations of MIF-positive expression rate with age,menstruation,tumor size,auxiliary lymph node metastasis,histological type and grade,and clinical stage of the breast cancer patients.We also compared MVD level and 5-year overall survival rate between MIF-positive patients and MIF-negative ones.Results The positive expression of MIF was correlated with HER2(+)subtype breast cancer and auxiliary lymph node metastasis (P < 0.05 ).The patients with MIF-positive expression had a significantly higher level of MVD than those with MIF-negative expression (P < 0.05 ). Kaplan-Meier method showed that MIF-positive patients had a poor prognosis than MIF-negative ones (Log-rank=1 9.5 1 6,P = 0.000).Conclusion Breast cancer patients with MIF-positive expression may be mostly of HER2 (+)subtype,and tend to develop auxiliary lymph node metastasis.These patients have a significantly higher level of MVD and poor prognosis than those with MIF-negative expression.

Expression and clinical significance of MIF and MMP-9 in gastric cancer / 安徽医科大学学报

Objective To investigate the expression and clinical significance of migration inhibitory factor ( MIF) and matrix metalloproteinase-9(MMP-9) in human gastric cancer tissue and corresponding adjacent normal tissue. Methods Selected surgery and pathologically confirmed 80 cases of gastric cancer as the experimental group, took another 80 cases of corresponding adjacent tissues as a control group. The expressions of MIF and MMP-9 were de-tected in 80 cases of gastric cancer patients cancer tissue and corresponding adjacent normal tissue by immunohisto-chemical SP method. Results ①The expression of MIF and MMP-9 of gastric cancer in varying degrees:The pos-itive rates of MIF and MMP-9 were 68. 8% and 67. 5%,which were higher than that in adjacent normal tissues, 32. 5% and 37.5% (P <0.05);② The expression of MIF was significantly associated with the clinical stage, depth of invasion,degree of differentiation,lymph node metastasis and TNM staging (P<0.05), nothing to do with other clinicopathological parameters;the expression of MMP-9 was significantly associated with the depth of inva-sion,degree of differentiation, lymph node metastasis and TNM staging (P<0.05), nothing to do with other clini-copathological parameters;③ There was positive correlation between the expression of MIF and MMP-9 in gastric cancer tissue (χ2 =9. 154, P<0. 01,r=0.338). Conclusion The expressions of MIF and MMP-9 show a posi-tive expression in gastric carcinoma, there maybe have a positive correlation between MIF and MMP-9. Their ex-pressions of varying degrees are closely related with the occurrence and development of gastric cancer, guidance gastric diagnosis, treatment and prognosis.

Estudos QSAR e Ancoragem Molecular de Inibidores da Atividade Biológica do Fator de Inibição da Migração dos Macrófagos (MIF) / QSAR Modeling and Molecular Docking Study of Inhibitors of Macrophage Migration Inhibitory Factor (MIF)

Cumarina e 4-Cromonas são promissores inibidores de fator inibição da migração de macrófagos (MIF), uma proteína envolvida em doenças inflamatórias, como artrite reumatóide e outras patologias. Estudos teóricos de QSAR e ancoragem molecular de um conjunto de compostos mostraram correlação com estudos experimentais. Os descritores doadores de ligação hidrogênio e momento dipolo total foram capazes de prever atividade inibitória de compostos contra o MIF (MIFi). Paralelamente, estudos de ancoragem molecular também foram capazes de identificar ligações hidrogênio e hidrofóbicas entre os ligantes e o MIF. Como resultado, ambas as metodologias mostraram as contribuições de ligação de hidrogênio e interações hidrofóbicas para explicar a atividade de compostos inibidores de MIF, descrevendo os grupos farmacofóricos destes compostos. Adicionalmente, um conjunto de cumarinas naturais e sintéticas foi submetido aos modelos QSAR e de ancoragem molecular a fim de que as suas atividades contra MIF fossem preditas. Ambas as metodologias de modelagem molecular puderam estimar as interações intermoleculares entre inibidores e a enzima, os quais foram muito similares a compostos descritos previamente. Estes resultados podem ser úteis para o desenho de novos compostos contra doenças inflamatórias como artrite reumatóide.

Coumarin and Chromen-4-one are promising inhibitors of Macrophage Migration Inhibitory Factor (MIF), a protein involved in rheumatoid arthritis and other inflammatory diseases. Quantum structure-activity relationship (QSAR) and docking theoretical studies were undertaken on a set of compounds of known activity and showed agreement with previous experimental studies. Two descriptors, hydrogen donor sites and the total dipole, were able to predict MIF inhibitory activity (MIFi). The docking studies corroborated the QSAR studies. As a result, both methods indicated contributions of hydrogen bonds and hydrophobic interactions that explain the activity of the MIF inhibitors, describing the pharmacophore groups these molecules. Additionally, a set of natural and synthetic coumarins was subjected to the QSAR and docking models in order to predict their possible MIF inhibitory activity. Both molecular modeling methods were able to estimate the intermolecular interactions between inhibitors and enzyme, which were very similar to those of previously described compounds. These results could be useful to design new compounds against inflammatory diseases such as rheumatoid arthritis.

Fator de inibição da migração de macrófagos e interleucina-6 na síndrome de esmagamento: analogia com gravidade?: Relato de casos / Macrophage migration inhibitory factor and interleukin-6 in crush syndrome: analogy with severity?: Case reports

JUSTIFICATIVA E OBJETIVOS: A síndrome de esmagamento é descrita como um conjunto de manifestações sistêmicas resultantes da lesão à célula muscular devida a pressão ou esmagamento. O fator de inibição da migração de macrófagos (MIF) é uma citocina multifuncional envolvida em amplo espectro de eventos patológicos relevantes para o sistema imune. A interleucina-6 (IL-6) é uma citocina pró-inflamatória envolvida nas fases precoces da resposta inflamatória por trauma e no desenvolvimento das fases precoce e tardia da disfunção orgânica múltipla (MODS). Há poucos estudos publicados sobre o perfil de citocinas na síndrome de esmagamento (SE). O objetivo deste trabalho foi relatar quatro casos de SE, avaliando os níveis séricos de MIF e IL-6 nestes pacientes e sua correlação com a gravidade. RELATO DOS CASOS: Foram estudados quatro pacientes internados no centro de terapia intensiva (CTI) do Hospital Central do Exército (HCE) com história de trauma que desenvolveram síndrome de esmagamento. O escore APACHE II foi realizado em cada paciente nas primeiras 24 horas de admissão no CTI. Foram coletadas amostras diárias de soro de cada um durante seis dias consecutivos e o escore SOFA foi aferido diariamente. Foram dosados no soro a creatinoquinase (CK) e as citocinas MIF e IL-6. Os dados foram analisados. CONCLUSÕES: Variações observadas nos níveis de CK foram acompanhadas por alterações nos níveis das citocinas inflamatórias bem como do escore SOFA, sugerindo interdependência entre essas variáveis. Estudos anteriores já haviam demonstrado resultado semelhante. Embora o emprego de citocinas como indicadores de gravidade no trauma possa ser assunto de interesse, há necessidade de estudos com amostragem maior para validar esta observação.

BACKGROUND AND OBJECTIVES: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine involved in a broad-spectrum pathological events relevant to the immune system. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS). Crush syndrome has been described as the systemic manifestation of muscle cell damage resulting from pressing or crushing. There are few data about MIF and IL-6 in crush syndrome. The aim of this study was to report four cases of crush syndrome, measuring seric levels of MIF and IL-6 and its correlation with severity. CASES REPORTS: Four patients suffering from crush syndrome after an accident with an explosive artifact were enrolled in the study. APACHE II score was checked at admission. It was collected serum sample of these patients during six consecutive days. Serum MIF, IL-6 and creatine kinase (CK) were measured. Sepsis-related organ failure assessment (SOFA) score was evaluated concomitantly. Data were analyzed. CONCLUSIONS: The variations observed in the CK measures were followed by alterations in the cytokines' level and at the SOFA score, suggesting interdependence between those factors. Other articles have already demonstrated similar results. Although the use of cytokines as biomarkers of severity in trauma is matter of interest, we need large studies with a higher number of patients to validate this observation.

Upregulation of Macrophage Migration Inhibitory Factor (MIF) Production from Peripheral Blood Mononuclear Cells (PBMCs) Stimulated by Tumor Necrosis Factor (TNF)-alpha in Patients with Behcet's Syndrome / 대한류마티스학회지

Objective: To investigate the effect of tumor necrosis factor (TNF)-alpha on the production of macrophage migration inhibitory factor (MIF), which might have important roles in the immune mediated inflammatory response of Behcet's syndrome. Methods: Sixty two patients with Behcet's syndrome and thirty healthy controls were included in this study. The concentrations of TNF-alpha in sera were determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMCs) from eleven patients with Behcet's syndrome were cultured for 48 hours with various concentration of TNF-alpha. The concentrations of MIF in sera and culture supernatants were determined by ELISA. Results: Serum levels of TNF-alpha were significantly higher in patients with Behcet's syndrome than in healthy controls. TNF-alpha dose-dependently increased MIF production from PBMCs in patients with Behcet's syndrome. Serum levels of TNF-alpha tended to correlate with serum levels of MIF, although did not reach statistical significance. Conclusion: Upregulation of MIF production by increased levels of TNF-alpha in patients with Behcet's syndrome might be related to the pathogenesis of Behcet's syndrome.

Macrophage Migration Inhibitory Factor (MIF) Induced Stromal Cell-derived Factor 1 (SDF-1) Production Via Nuclear Factor KappaB (NF-kappaB) Signaling in Rheumatoid Arthritis Fibroblast Like Synoviocytes (RA-FLS)

BACKGROUND: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. METHODS: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. RESULTS: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-kappaB. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-kappaB- mediated pathways. CONCLUSION: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.

The Expression of Proinflammatory Cytokine and Macrophage Migration Inhibitory Factor in a Rat Lipopolysaccharide-Induced Cystitis Model / 대한비뇨기과학회지

PURPOSE: We wanted to evaluate the changes of the expression of macrophage migration inhibitory factor(MIF) according to time, so we determined the semiquantitative score from immunostaining in a bladder inflammatory rat model. MATERIALS AND METHODS: A total of 25 female Sprague-Dawley rats were divided into 5 groups according to the time course. Group 1 was the control group that was treated with an intravesical instillation of saline. Groups 2-5 were evaluated at 4 hours, 24 hours, 48 hours and 7 days after the instillation of lipopolysaccharide(LPS), respectively. H&E staining and immunohistochemical staining for MIF were performed after removing the bladder. A semiquantitative score was used to evaluate the cystitis(bladder inflammation score; BIS). The expression of MIF in the bladder was graded from 0 to 3+(MIF score; MIFS). RESULTS: The staining of MIF was the most intense in the basal layer of the urothelium in the control group(BIS 0, MIFS 3). The degree of bladder inflammation was highest in group 3, and MIF was not expressed even in the urotherlium without inflammation(BIS 2.2, MIFS 0.6). The bladder inflammation was decreased after 48 hours, and the expression of MIF was increased after 48 hous(BIS 1.7, MIFS 1.6). The severity of bladder inflammation and the expression of MIS were significantly changed with the time course(p<0.001). CONCLUSIONS: These results suggest that pre-formed MIF is stored in the cytoplasm of the basal cells in the urothelium, and it is released into the lumen of the bladder after a noxious stimulus like LPS.